The present invention relates to methods and compositions for the treatment and prophylaxis of arteriosclerosis and/or xanthoma.
Throughout the world, in recent years, the tendency has been for the incidence of coronary artery disease and arteriosclerosis, including atherosclerosis, to increase, even in those countries in which hitherto they have not been prevalent. Amongst the factors implicated in such an increase are changes in lifestyle, including the "Western" meat-rich diet, and the adoption of such a diet even in countries where it is not traditional, and the general increase in the average age of the population. As a result, these diseases and arteriosclerosis, in particular, are widely feared as arteriosclerosis is a well known potential cause of unexpected death, for example by such sequelae of arteriosclerosis as myocardial infarction.
One of the main risk factors implicated in these diseases is a high blood plasma lipid level, particularly a high blood plasma cholesterol level. There have, therefore, been many attempts to use an agent which lowers the cholesterol level in order to prevent and cure these diseases, and many compounds have been developed which, to a greater or lesser extent, have this effect. For example, one such compound, which has been very successful and is very well known is pravastatin, which is a lipid regulating agent and is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (hereinafter referred to as "HMG-CoA reductase inhibitor") which is believed to act on the rate-determining step of cholesterol biosynthesis. It has been reported that coronary arteriosclerosis and xanthoma may be prevented in rabbits receiving pravastatin, but its efficacy remains insufficient [Biochimica et Biophysica Acta, 960, 294-302 (1988)]. Studies to control coronary arteriosclerosis and xanthoma have been carried out using a combination of two lipid regulating agents, pravastatin and cholestyramine, which is well known as an agent for lowering lipoprotein levels, but the efficacy of this combination also remains insufficient [Atherosclerosis, 83, 69-80 (1990)].
It has been proposed in Japanese Patent Kokai Application No. Hei 7-41423 that a specific class of insulin resistance-improving agents, for example troglitazone, may be effective in the treatment and prophylaxis of arteriosclerosis, particularly atherosclerosis, but, again, the efficacy of such compounds is not quite satisfactory.